Autor: Vlk, M.; Urban, M.; Elbert, T.; Sarek, J.
Název práce v češtině: Syntéza selektivně deuterovaných a tritiovaných lupanových derivátů s cytotoxickou aktivitou.
Název práce v angličtině: Synthesis of selectively deuterated and tritiated lupane derivatives.
Studentská publikace: ne
Klíčová slova v češtině: Izotopické značení, tritium, deuterium.
Klíčová slova v angličtině: Isotopic labelling, Tritium, Deuterium.
Abstrakt česky: Syntetizovali jsme deuterované a tritiované analogy vysoce oxidovaných lupanových derivátů z naší skupiny, které dříve vykázaly vysoké protinádorové aktivity, abychom mohli dále studovat jejich mechanizmus účinku. Podrobněji viz abstrakt v anglickém jazyce.
Abstrakt anglicky: The aimof this work was to synthesize deuterated and tritiated analogues of highly oxidized lupane derivatives known from our group. We selected compounds that previously showed very high cytotoxic activity on multiple cancer cell lines in order to further investigate themechanismof their action. From startingmaterial (compounds 1–4), we obtained benzyl platanate (5) and its reaction with deuteromethyltriphenylphosphonium iodide gave deuterated compound 6. Following benzyl deprotection gave free acid 7 and oxidation with SeO2 gave 30-oxo-[29-2H2]lup-20(29)-en-28-oic acid (8), which is one of themost active compounds synthesized in our group to date (IC50 6 lmol/L on CEM cell line). The alkylation of benzyl 2-hydroxy-3-oxolupa-1,20(29)-dien-28-oate (9) with methyliodide or deuteromethyliodide followed by a series of deprotection and hydrogenation steps gave compounds 10–14, where 2b-[31-2H3]methoxy-3-oxolupan-20(29)-en-28-oic acid (13) is especially interesting, it showed lower activity on CEMcell line (IC50 10 lmol/L) however, it was very active against Ph1—positive human leukemia BV-
173 (IC50 0.91 lmol/L) and against human myelogenous leukemia K562 (IC50 0.52 lmol/L). Selectively labelled [3a-2H] and [3a-3H] methyl 3b-acetoxy-21,22-dioxolup-18-en-28-oates 24, 25 were prepared in three steps by reduction of corresponding 3-oxo derivatives and they showed moderate activity on CEM cell line (IC50 10 lmol/L). In total, 11 labelled compounds (6–8, 11, 14, 18, 19, 21, 22, 24 and 25) have not been reported before.
Jazyk v originále: anglický
Název časopisu: J. Radioanal. Nucl. Chem.
Rok: 2013
Svazek (ročník): 298
Číslo časopisu v rámci uvedeného svazku: 2
Strana od-do: 1149-1157

Q1: ne

ISSN časopisu: 0236-5731
Vydavatel: Springer Science+Business Media
Způsob financování: Czech Sci. Found. (305/09/1216), MSM 6840770040; SGS 10/212/OHK4/2T/14